PXD044898-1

PXD044898 is an original dataset announced via ProteomeXchange.

Title	DUSP8 dephosphorylates Pur-alpha
Description	Dual-specificity phosphatase 8 is a MAPK phosphatase that dephosphorylates and inactivates the kinase JNK. DUSP8 is highly expressed in T cells; however, the in vivo role of DUSP8 in T cells remains unclear. Using T-cell-specific DUSP8 conditional knockout (T-DUSP8 cKO) mice, mass spectrometry analysis, chromatin-immunoprecipitation sequencing, and immune analysis, we found that DUSP8 interacted with Pur-α, stimulated interleukin-9 (IL-9) gene expression, and promoted Th9 differentiation. Mechanistically, DUSP8 dephosphorylated the transcriptional repressor Pur-α upon TGF-β signaling, leading to the nuclear export of Pur-α and subsequent IL-9 transcriptional activation. Furthermore, IL-9 mRNA levels were induced in Pur-α-deficient T cells. In addition, T-DUSP8 cKO mice displayed reduction of IL-9 and Th9-mediated immune responses in the allergic asthma model. Reduction of IL-9 mRNA levels in T cells and allergic responses of T-DUSP8 cKO mice was reversed by Pur-α knockout. Remarkably, DUSP8 protein levels and the DUSP8–Pur-α interaction were indeed increased in the cytoplasm of T cells from human asthma patients and atopic dermatitis patients. Collectively, DUSP8 induces TGF-β-stimulated IL-9 transcription and Th9-induced allergic responses by inhibiting the nuclear translocation of the transcriptional repressor Pur-α. DUSP8 may be a T-cell biomarker and therapeutic target for asthma and atopic dermatitis.
HostingRepository	PRIDE
AnnounceDate	2023-09-30
AnnouncementXML	Submission_2023-09-30_06:51:07.172.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Huai-ChiaChuang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-27 21:19:03	ID requested
⏵ 1	2023-09-30 06:51:07	announced
2	2023-11-14 09:02:56	announced	2023-11-14: Updated project metadata.

submitter keyword: Pur-alpha, in vitro phosphatase assay,DUSP8

Tse-HuaTan
contact affiliation	National Health Research Institutes, Taiwan
contact email	ttan@nhri.edu.tw
lab head
Huai-ChiaChuang
contact affiliation	Immunology Research Center, National Health Research Institutes
contact email	cinth@nhri.org.tw
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044898
     1. Label: PRIDE project
     2. Name: DUSP8 dephosphorylates Pur-alpha